Pilot of Abatacept-based Immunosuppression for Prevention of Acute GvHD During Unrelated Donor HCT

Inclusion Criteria:

1. Patients with AML, with or without a history of myelodysplastic syndrome in one of the following categories.

   (a) Patients in first complete remission with high-risk features
2. Patients with ALL, in either of the following categories:

   1. In 2nd or greater complete remission (complete remission is defined as \> 5% blasts in marrow)
   2. Delayed 1st CR-Failure to achieve complete remission after a single round of induction therapy
3. Patients with undifferentiated or biphenotypic leukemia in 1st or greater complete remission.
4. Patients with Myelodysplastic Syndrome(s) with an IPSS score of \>1.5 and \<10% blasts in the bone marrow at the time of transplant. These conditions will include:

   1. Refractory anemia
   2. Refractory anemia with ringed sideroblasts
   3. Refractory cytopenia with multilineage dysplasia
   4. Refractory cytopenia with multilineage dysplasia and ringed sideroblasts
   5. Refractory anemia with excess blasts-1 (5-10% blasts)
   6. Refractory anemia with excess blasts-2 (10-20% blasts)
   7. Myelodysplastic syndrome, unclassified
   8. MDS associated with isolated del (5q)
   9. Patients diagnosed with AML in CR1 after an initial diagnosis of MDS.
5. Age 12 years or older.
6. No prior allogeneic transplant
7. Karnofsky performance score or Lansky Play-Performance of at least 80.
8. Signed informed consent for adults and for minors the provision of pediatric assent and parental permission.

Exclusion Criteria:

1. Age \<12 years old.
2. Patients requiring \>2 courses of induction chemotherapy to achieve remission status.
3. HIV infection
4. Tuberculosis Infection
5. Chronic Obstructive Pulmonary Disease
6. Pregnancy (positive serum b-HCG) or breastfeeding
7. Creatinine clearance or nuclear medicine GFR of \< 50 mL/min
8. Cardiac ejection fraction \< 50%
9. bilirubin \> 2 × upper limit of normal or ALT \> 4 × upper limit of normal or unresolved veno-occlusive disease.
10. Pulmonary disease with FVC, FEV1 or DLCO parameters \<45% predicted (corrected for hemoglobin) or O2 saturation \<92% on room air.
11. Karnofsky performance score or Lansky Play-Performance Scale \<80
12. Uncontrolled viral, bacterial, or fungal infection at the time of study enrollment
13. Availability of a willing and fully MHC-matched related donor.
14. Positive cytotoxic recipient-donor cross-match or positive HLA antibody screen against donor-disparate antigens.
15. Any active infection.
16. Unable to obtain informed consent.